Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders

Early Phase 1

Completed

• Conditions: Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency; Carnitine Palmitoyltransferase Deficiency 2; Trifunctional Protein Deficiency; Very Long Chain Acyl Coa Dehydrogenase Deficiency
• Interventions: Dietary Supplement: Isocaloric Placebo Supplement; Dietary Supplement: Nutritional Ketone Supplement

• Registration Number: NCT05411835
• Lead Sponsor: Oregon Health and Science University

Brief Summary

The purpose of the study is to determine if an oral ketone beverage is safe and well-tolerated during moderate intensity exercise in participants with long-chain fatty acid oxidation disorders and if it will raise blood ketones to levels similar to that reported among normal healthy subjects.

Detailed Description

Purpose: Subjects with long-chain fatty acid oxidation disorders (LC-FAOD) do not make ketones during fasting or with exercise. Ketones are an important alternative energy substrate during moderate exercise, sparing the oxidation of glucose and providing a source of ATP to the central nervous system and exercising muscle. Fatty acid oxidation in the liver is required to make ketones. Subjects with a LC-FAOD cannot generate ketones because of their block in fatty acid oxidation during exercise. Providing ketones in an oral ketone beverage may increase blood ketones with exercise to levels normally observed in humans.

Aim: To determine the safety and tolerability of an oral ketone beverage during moderate intensity exercise among subjects with a LC-FAOD compared to an isocaloric maltodextrin beverage, and to determine blood ketone concentrations.

Hypothesis: Oral consumption of a ketone beverage before moderate intensity exercise will be safe and well-tolerated, and will raise blood ketones among subjects with a LC-FAOD to concentrations similar to that reported in the literature among normal healthy subjects.

Study Timeline

• Study First Submitted: 2022-05-27
• Study First Submitted QC: 2022-06-06
• Study First Posted: 2022-06-09
• Study Start: 2022-08-01
• Status Verified: 2022-10
• Primary Completion: 2023-01-31
• Study Completion: 2024-01-22
• Last Update Submitted: 2024-04-01
• Last Update Posted: 2024-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• confirmed diagnosis of VLCAD, LCHAD/TFP or CPT2 deficiency
• speak English
• willing to complete 2 moderate intensity exercise treadmills

Exclusion Criteria

• subjects actively participating in another research study that prohibits their participation
• pregnant females
• subjects with diabetes or taking medications to treat diabetes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Isocaloric Placebo Supplement	Isocaloric Placebo Supplement	The maltodextrin pre-exercise beverage is a nutritional supplement. The supplement will be provided by Nestle as powered sachets to mix in water. It contains an isocaloric amount of maltodextrin, flavors and stevia similar to the ketone beverage.
Nutrition Ketogenic Supplement	Nutritional Ketone Supplement	The Ketone pre-exercise beverage is a nutritional supplement. The supplement will be provided by Nestle as powered sachets to mix in water. It contains a mix of D-beta-hydroxybutyrate salts, flavors and stevia.

Primary Outcome Measures

Name	Time	Method
Adverse Events- type	2 hours after product intake	Description of Adverse events: categorical
Abdominal discomfort	2 hours after product intake	visual analogue scale (VAS) 0-10
Gastric reflux	2 hours after product intake	visual analogue scale (VAS) 0-10
Nausea	2 hours after product intake	visual analogue scale (VAS) 0-10
Adverse Events- incidence	2 hours after product intake	Number of Adverse events
Adverse Events- severity	2 hours after product intake	Severity of adverse event: grade 1-5
Adverse Events- causal relationship	2 hours after product intake	Yes/No related to product intake
Decreased appetite	2 hours after product intake	visual analogue scale (VAS) 0-10
Diarrhea	2 hours after product intake	visual analogue scale (VAS) 0-10
Headache	2 hours after product intake	visual analogue scale (VAS) 0-10

Secondary Outcome Measures

Name	Time	Method
Blood Ketones	20 minutes after moderate intensity exercise	plasma beta-hydroxybutyrate concentration
Blood Lactate	20 minutes after moderate intensity exercise	serum lactate concentration
Respiratory Exchange Ratio	peak 40 minute exercise	VCO2/VO2 0.7 - 1.0
Heart Rate	peak 40 minute exercise	beats per minute
Blood Glucose	20 minutes after moderate intensity exercise	serum glucose
Blood Creatine Kinase	20 minutes after moderate intensity exercise	plasma CK concentration
Blood Pressure	peak 40 minute exercise	systolic BP
Perceived exertion	peak 40 minute exercise	Borg scale 1-20

Trial Locations

Locations (1)

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States